We are investigating the natural history of the receptors for immunoglobulin E (IgE) and immunoglobulin E (IgG) on mast cells and basophils. We aim to study the mode of function and turnover of the free and ligand bound receptors and the fate of the cell bound IgE before, during and after exocytosis of mediators of the allergic response which is initiated by aggregation of surface bound IgE. We found that monomeric IgE molecules remain resident on the cell surface for over 250 hours and endocytosis is only affected by cross-linking of surface bound molecules. The minimal size aggregate required to signal internalization was dimeric. Interestingly, dimers provide only a poor signal for histamine release from RBL cells. Internalized IgE is later released, the receptor internalizes with the ligand and does not appear to be reusable. Unlike the process of mediator release, internalization of aggregated IgE by RBL and normal mast cells is independent of calcium and proceeds at a different rate. Release and coendocytosis were found to be responsive to various pharmacological agents differently from endocytosis but similarly to each other. The rate of internalization is the same for normal mast cells and RBL cells. Empty receptors for IgE and monomeric IgE cointernalize with crosslinked IgE. Cell bound aggregated IgG is endocytosed. Monomeric receptor-bound IgE recycles to the cell surface. Binding protects the IgE and the receptor from degradation. When cells are allowed to bind aggregated IgE as well as IgG, the endocytosis of either is unaltered. Additionally, endocytosis of aggregated IgG has no effect on monomerically bound IgE. Unlike the receptor for IgE, the receptor for IgG might be multimeric. It is hoped that further clarification of these aspects of mast cell and basophil function will lead to better understanding of the allergic response.